Preterm Rupture of MembranesPROMPTNCT04878978
Premature Rupture Membranes and tPTL: a Personalised Approach (PROMPT)
A study testing Amniocentesis and Routine care without amniocentesis in people with Preterm Rupture of Membranes and Threatened Preterm Labor, run by Chelsea and Westminster NHS Foundation Trust.
Trial summary
Preterm birth (less than 37 weeks) affect approximately 8% of babies in the UK and is the worldwide leading cause of death in children under the age of 5. Subclinical infection affects approximately 50% of women giving birth before 32 weeks. Infection contributes to significant neonatal morbidity and mortality. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Preterm Rupture of Membranes, Threatened Preterm Labor
- What is being tested?
- Amniocentesis and Routine care without amniocentesis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 276 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2021to 1 Jun 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pregnant women between 23+0 weeks and 34 weeks gestation.
- Admitted with signs and symptoms of threatened PTL with positive fetal fibronectin of 200ng/mL or clinical confirmation of preterm rupture of membranes
- Singleton pregnancy
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements.
- Women must be aged 18 years or older.
- -
Who cannot join
- Chorioamnionitis: Defined as maternal temperature was elevated to 37.8°C and two or more of the following criteria were present: uterine tenderness, malodorous vaginal discharge, maternal leucocytosis (>15 000 cells/mm3), maternal tachycardia (>100 beats/min) and fetal tachycardia (>160 beats/min).
- Multiple pregnancy
- Uterine contractions >2:10 and evidence on tocogram
- Maternal infections such as HIV and hepatitis
- Clinical suspicion of placental abruption
- Evidence of meconium stained liquor
Show all 10Show fewer
- Fetal abnormality or growth restriction
- Abnormal fetal heart rate pattern
- Maternal pathologies in which preterm termination of pregnancy is required.
- -
About this study
Official title: A Randomised Study of a Personalised Approach to the Management of Preterm Rupture of Membranes and Threatened Preterm Labour
Preterm birth (less than 37 weeks) affect approximately 8% of babies in the UK and is the worldwide leading cause of death in children under the age of 5. Subclinical infection affects approximately 50% of women giving birth before 32 weeks. Infection contributes to significant neonatal morbidity and mortality. Antibiotics such as erythromycin is currently used to treat women who present with preterm rupture of membranes. While this has shown short-term improvement in neonatal morbidity, it has not had any impact in reducing the perinatal mortality and also little effect on the health of the children at age seven. Some antibiotics such as co-amoxiclav has not shown to be effective in delaying delivery and some studies have shown that antibiotics increases rather than reduces the risk of cerebral palsy. Many women do not display signs of infection and the underlying bacteria is multifactorial (bacterial vaginosis, trichomoniasis, gonorrhoea, Chlamydia, ureaplasma, Group B streptococcal and E. Coli) and remains a diagnostic challenge. The only available clinical approach is to test the sample of amniotic fluid for bacteria and small case series have shown prolongation of pregnancy when accurately targeted antibiotic treatment is used.
This research aims to prove that targeted antibiotic therapy results in a greater prolongation of pregnancy than standard management for women with preterm prelabour rupture of membranes (PPROM) and/or threatened preterm labour (tPTL).
Women will be randomised to standard care versus BioFire directed antibiotic treatment in addition to standard care. Investigators will use the BioFire point of care testing to identify the presence of infection and identify with anti-microbial resistance genes the bacteria possess to guide the antibiotic treatment. To be certain that the presence of infection is detected the investigators will use PCR to test the amniotic fluid for IL-6 and white cell count.
Read the detailed description
Overall 10-15% of women delivering before 37 weeks have intraamniotic infection and of those delivering before 32 weeks have 50% chance. Consequently, since infection is one of the most important causes of spontaneous PTL it is possible that antibiotic treatment may delay delivery and reduce the risk of fetal damage and consequently long-term disability. However, most cases do not display typical symptoms or signs of infection, the only way to make the diagnosis reliably is through performing an amniocentesis. The risk of this procedure is low in the 3rd trimester and should be considered particularly in those in PTL at less than 32 weeks, when the risk of infection is high. Studies in non-human primate models of intra-amniotic infection support for this approach, showing that specific antibiotic therapy can prevent infection-induced PTL and prolong pregnancy with improved neonatal outcomes.
Human studies have been less positive, with antibiotics failing to prolong pregnancy in PTL or eradicate infection in PPROM. The Oracle trial assessed the ability of two antibiotics, erythromycin and co-amoxiclav, to reduce the risk of PTD in women with PPROM using a composite primary outcome of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Erythromycin, but not co-amoxiclav, reduced the risk of the primary outcome.
Two recent papers have challenged this negative view of the use of antibiotics for intraamniotic infection. In the first, amniocentesis was performed to identify infection or inflammation and broad-spectrum antibiotics administered to women with a singleton pregnancy presenting with tPTL at between 20 and 34 weeks. Infection was thought to be present in at least 60% of cases as judged by the presence of a raised WCC, although only 20% had positive cultures using standard microbiological approaches. 100% had an elevated IL-6 level confirming inflammation. Repeat amniocentesis confirmed resolution of inflammation in all cases and overall average prolongation was 11.4 days. In a control group not given antibiotics average prolongation was 3 days. In 3 cases infection was shown to be cleared by antibiotic treatment. In the second report, women undergoing rescue cerclage had an amniocentesis and those found to have evidence of infection or inflammation treated with broad spectrum antibiotics. A repeat amniocentesis demonstrated resolution of infection/inflammation with antibiotic treatment.
Investigators plan to recruit women to a multicenter randomised trial of standard management vs. amniocentesis with the use of BioFire filmArray point of care testing to identify the presence of bacteria and identify common anti-microbial resistance genes the bacteria possess to guide the selection of an additional antibiotic agent.
The BioFire filmArray clinical application is currently being studied in patients with pneumonia in the INHALE study. Investigators plan to use the BioFire filmArray in a maternity setting and will use the information generated by the BioFire filmArray platform to give targeted antibiotics in the amniocentesis arm in addition to routine erythromycin with the aim of prolonging latency to delivery and of improving neonatal outcome.
- Being tested
- Amniocentesis, Routine care without amniocentesis
- Medical subject headings
- Fetal Membranes, Premature Rupture
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmniocentesisDiagnostic test
Amniocentesis will be used to sample the amniotic fluid for Biofire detection of microorganism and to direct antibiotic treatment
Routine care without amniocentesisOther
Routine clinical care
| Study group | Role | What they receive |
|---|---|---|
| Routine care | Active comparator | Women who present with PPROM or threatened PTL and have routine care Receives: Other: Routine care without amniocentesis |
| Amniocentesis and biofire directed antibiotic use | Experimental | Women who present with PPROM or threatened PTL and randomised to amniocentesis and biofire directed antibiotic treatment Receives: Diagnostic Test: Amniocentesis |
What is being measured
The primary outcome is the main question the study is designed to answer.
The length of latency of women receiving amniocentesis with BioFire filmArray POC test guided antibiotic selection compared to those receiving standard treatment.
Days
Measured: 4 years
Secondary outcomes (9)
Maternal outcome
The number of women with (i) clinical diagnosis of infection including: chorioamnionitis (one or more of pyrexia, abdominal pain/tenderness, tachycardia, vaginal discharge) or (ii) postpartum endometritis with laboratory diagnosis (raised peripheral blood CRP and/or WCC, positive blood, vaginal or urine cultures)
Measured: 4 years
Neonatal outcome
We will use a composite severe neonatal outcome of neonatal death, major adverse outcome ie, chronic lung disease (defined as the need for supplementary oxygen at 36 weeks post conception) major cerebral abnormality on ultrasonography identified prior to discharge or necrotising enterocolitis.
Measured: 4 years
Microbiota and inflammatory marker endpoints
Maternal (vaginal, rectal, amniotic fluid) and neonatal (faecal) (measured using BioFire PCR, 16srRNA sequencing, multiplex ELISA, and associated clinical tests). Residual sample stored for future peptide/proteomics testing (e.g. MALDI-TOF multiplex). Incidence of antibiotic resistance (neonatal and maternal).
Measured: 4 years
Patient based endpoints
Acceptability of having an amniocentesis; how risks communicated and understood; how test presented; how was the situation understood by the researchers/care givers and how did that impact on the subject's ability to understand what was being proposed? Partner perceptions and sense of inclusion/involvement.
- Clinical data including previous obstetric history, demographic and socio-economic data and neonatal health data, the gestational age and cervical dilatation at randomisation, other drugs prescribed (corticosteroids, indomethacin, nifedipine, magnesium sulphate) will be collected.
Measured: 5 years
Timing of birth
Number of women who deliver within 2 days
Measured: 4 years
Mode of delivery
Vaginal, caesarean or assisted birth
Measured: 5 years
Length of hospitalisation
Number of days of maternal hospitalisation
Measured: 4 years
Gestational age at delivery
Weeks
Measured: 4 years
Outcomes for neonates admitted to NICU
Number of neonates (i) admitted to NICU, (ii) ventilated, (iii) needing oxygen (iv) respiratory distress syndrome; (v) treatment with exogenous surfactant and (vi) with infection
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2021
- Study start1 Sep 2021 (estimated)
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Preterm Rupture of MembranesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a single centre open labelled randomised study.
- Masking
- None (open label)
- Enrolment
- 276 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chelsea and Westminster NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04878978
- Sponsor's protocol ID
- C&W20/21
- Acronym
- PROMPT
- Status last verified
- Apr 2021
- First submitted
- 20 Apr 2021
- Last updated
- 18 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Study of a Personalised Approach to the Management of Preterm Rupture of Membranes and Threatened Preterm Labour
- ClinicalTrials.gov ID
- NCT04878978
- Acronym / sponsor ID
- PROMPT / C&W20/21
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 276 participants (estimated)
- Lead sponsor
- Chelsea and Westminster NHS Foundation TrustUniversity, hospital or other
- Study start
- 1 Sep 2021 (estimated)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 10 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Preterm birth (less than 37 weeks) affect approximately 8% of babies in the UK and is the worldwide leading cause of death in children under the age of 5. Subclinical infection affects approximately 50% of women giving birth before 32 weeks. Infection contributes to significant neonatal morbidity and mortality. Antibiotics such as erythromycin is currently used to treat women who present with preterm rupture of membranes. While this has shown short-term improvement in neonatal morbidity, it has not had any impact in reducing the perinatal mortality and also little effect on the health of the children at age seven. Some antibiotics such as co-amoxiclav has not shown to be effective in delaying delivery and some studies have shown that antibiotics increases rather than reduces the risk of cerebral palsy. Many women do not display signs of infection and the underlying bacteria is multifactorial (bacterial vaginosis, trichomoniasis, gonorrhoea, Chlamydia, ureaplasma, Group B streptococcal and E. Coli) and remains a diagnostic challenge. The only available clinical approach is to test the sample of amniotic fluid for bacteria and small case series have shown prolongation of pregnancy when accurately targeted antibiotic treatment is used.
This research aims to prove that targeted antibiotic therapy results in a greater prolongation of pregnancy than standard management for women with preterm prelabour rupture of membranes (PPROM) and/or threatened preterm labour (tPTL).
Women will be randomised to standard care versus BioFire directed antibiotic treatment in addition to standard care. Investigators will use the BioFire point of care testing to identify the presence of infection and identify with anti-microbial resistance genes the bacteria possess to guide the antibiotic treatment. To be certain that the presence of infection is detected the investigators will use PCR to test the amniotic fluid for IL-6 and white cell count.
Detailed description
Overall 10-15% of women delivering before 37 weeks have intraamniotic infection and of those delivering before 32 weeks have 50% chance. Consequently, since infection is one of the most important causes of spontaneous PTL it is possible that antibiotic treatment may delay delivery and reduce the risk of fetal damage and consequently long-term disability. However, most cases do not display typical symptoms or signs of infection, the only way to make the diagnosis reliably is through performing an amniocentesis. The risk of this procedure is low in the 3rd trimester and should be considered particularly in those in PTL at less than 32 weeks, when the risk of infection is high. Studies in non-human primate models of intra-amniotic infection support for this approach, showing that specific antibiotic therapy can prevent infection-induced PTL and prolong pregnancy with improved neonatal outcomes.
Human studies have been less positive, with antibiotics failing to prolong pregnancy in PTL or eradicate infection in PPROM. The Oracle trial assessed the ability of two antibiotics, erythromycin and co-amoxiclav, to reduce the risk of PTD in women with PPROM using a composite primary outcome of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Erythromycin, but not co-amoxiclav, reduced the risk of the primary outcome.
Two recent papers have challenged this negative view of the use of antibiotics for intraamniotic infection. In the first, amniocentesis was performed to identify infection or inflammation and broad-spectrum antibiotics administered to women with a singleton pregnancy presenting with tPTL at between 20 and 34 weeks. Infection was thought to be present in at least 60% of cases as judged by the presence of a raised WCC, although only 20% had positive cultures using standard microbiological approaches. 100% had an elevated IL-6 level confirming inflammation. Repeat amniocentesis confirmed resolution of inflammation in all cases and overall average prolongation was 11.4 days. In a control group not given antibiotics average prolongation was 3 days. In 3 cases infection was shown to be cleared by antibiotic treatment. In the second report, women undergoing rescue cerclage had an amniocentesis and those found to have evidence of infection or inflammation treated with broad spectrum antibiotics. A repeat amniocentesis demonstrated resolution of infection/inflammation with antibiotic treatment.
Investigators plan to recruit women to a multicenter randomised trial of standard management vs. amniocentesis with the use of BioFire filmArray point of care testing to identify the presence of bacteria and identify common anti-microbial resistance genes the bacteria possess to guide the selection of an additional antibiotic agent.
The BioFire filmArray clinical application is currently being studied in patients with pneumonia in the INHALE study. Investigators plan to use the BioFire filmArray in a maternity setting and will use the information generated by the BioFire filmArray platform to give targeted antibiotics in the amniocentesis arm in addition to routine erythromycin with the aim of prolonging latency to delivery and of improving neonatal outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a single centre open labelled randomised study.
| Arm | Type | Receives |
|---|---|---|
| Routine care | Active comparator | Other: Routine care without amniocentesisWomen who present with PPROM or threatened PTL and have routine care |
| Amniocentesis and biofire directed antibiotic use | Experimental | Diagnostic Test: AmniocentesisWomen who present with PPROM or threatened PTL and randomised to amniocentesis and biofire directed antibiotic treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Pregnant women between 23+0 weeks and 34 weeks gestation.
- Admitted with signs and symptoms of threatened PTL with positive fetal fibronectin of 200ng/mL or clinical confirmation of preterm rupture of membranes
- Singleton pregnancy
- The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements.
- Women must be aged 18 years or older.
Key exclusion criteria (10 listed)
- Chorioamnionitis: Defined as maternal temperature was elevated to 37.8°C and two or more of the following criteria were present: uterine tenderness, malodorous vaginal discharge, maternal leucocytosis (>15 000 cells/mm3), maternal tachycardia (>100 beats/min) and fetal tachycardia (>160 beats/min).
- Multiple pregnancy
- Uterine contractions >2:10 and evidence on tocogram
- Maternal infections such as HIV and hepatitis
- Clinical suspicion of placental abruption
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmniocentesisAmniocentesis will be used to sample the amniotic fluid for Biofire detection of microorganism and to direct antibiotic treatment | Diagnostic test | Amniocentesis and biofire directed antibiotic use |
| Routine care without amniocentesisRoutine clinical care | Other | Routine care |
Primary outcome
The length of latency of women receiving amniocentesis with BioFire filmArray POC test guided antibiotic selection compared to those receiving standard treatment.
Time frame: 4 years
Days
9 secondary outcomes
Maternal outcome
Time frame: 4 years
Neonatal outcome
Time frame: 4 years
Microbiota and inflammatory marker endpoints
Time frame: 4 years
Patient based endpoints
Time frame: 5 years
Timing of birth
Time frame: 4 years
Mode of delivery
Time frame: 5 years
Length of hospitalisation
Time frame: 4 years
Gestational age at delivery
Time frame: 4 years
Outcomes for neonates admitted to NICU
Time frame: 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Amniocentesis and Routine care without amniocentesis in people with Preterm Rupture of Membranes and Threatened Preterm Labor, run by Chelsea and Westminster NHS Foundation Trust.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The length of latency of women receiving amniocentesis with BioFire filmArray POC test guided antibiotic selection compared to those receiving standard treatment. (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2021.